Six-transmembrane epithelial antigen of prostate 2 (STEAP2), also known as STEAP-2, metalloreductase STEAP2, prostate cancer-associated protein 1, protein up-regulated in metastatic prostate cancer, SixTransMembrane protein of prostate 1 (STAMP1), and 098P4B6, is an integral, six-transmembrane-spanning protein, which is upregulated in normal and malignant prostate cells. STEAP2, which works as a shuttle between the Golgi complex and the plasma membrane, is a metalloreductase which reduces iron and copper, facilitating their import into the cell. STEAP2 is mainly localized to epithelial cells of the prostate. STEAP2 is also expressed in normal heart, brain, pancreas, ovary, skeletal muscle, mammary gland, testis, uterus, kidney, lung, trachea, colon, and liver. STEAP2 is over-expressed in cancerous tissues, including prostate, bladder, cervix, lung, colon, kidney, breast, pancreatic, stomach, uterus, and ovarian tumors (Gomes, I. M. et al., 2012, Mol. Cancer Res. 10:573-587; Challita-Eid—P. M., et al., 2003, WO 03/087306; Emtage, P. C. R., 2005, WO 2005/079490).
CD3 is a homodimeric or heterodimeric antigen expressed on T cells in association with the T cell receptor complex (TCR) and is required for T cell activation. Functional CD3 is formed from the dimeric association of two of four different chains: epsilon, zeta, delta and gamma. The CD3 dimeric arrangements include gamma/epsilon, delta/epsilon and zeta/zeta. Antibodies against CD3 have been shown to cluster CD3 on T cells, thereby causing T cell activation in a manner similar to the engagement of the TCR by peptide-loaded MHC molecules. Thus, anti-CD3 antibodies have been proposed for therapeutic purposes involving the activation of T cells. In addition, bispecific antibodies that are capable of binding CD3 and a target antigen have been proposed for therapeutic uses involving targeting T cell immune responses to tissues and cells expressing the target antigen.
Antigen-binding molecules that target STEAP2, including antibody-drug conjugates, as well as bispecific antigen-binding molecules that bind both STEAP2 and CD3 would be useful in therapeutic settings in which specific targeting and T cell-mediated killing of cells that express STEAP2 is desired.